Activity of the novel immunomodulatory compound tucaresol against experimental visceral leishmaniasis

Tucaresol, a novel immunomodulator, was inactive against Leishmania donovan i amastigotes in both peritoneal and hone marrow macrophages in vitro at co ncentrations between 100 and 1 mu M, with toxicity to macrophages and paras ites at 300 mu M. However, against L. donovani in BALB/c mice at doses betw een 80 and 1.25 mg/kg of body weight administered once daily by the oral ro ute during days 7 to 11 of infection, an optimal dose of 5 mg/kg produced a 43.8 to 62.4% suppression of liver amastigotes, with significantly reduced activity at the extremes of the dose range. This response was not related to levels of infection. No interaction with the standard pentavalent antimo nial sodium stibogluconate (Pentostam) was observed during this period of i nfection. The optimum dose of 5 mg/kg was ineffective when administered dur ing the first week of infection and was most effective against the liver in fection when administered during weeks 2 to 3 of infection (42.3 to 46.8% i nhibition) and against the splenic infection when administered during week 6 of infection (59.5% inhibition). The optimum dose of tucaresol against L. donovani in C57BL/6 mice was 5 mg/kg, which produced a 40.8 to 48.7% suppr ession of liver amastigotes when administered in a range of 80 to 1.25 mg/k g during days 7 to 11 of infection. The drug had no activity against L. don ovani infections in C.B-17 scid mice when the same regimen aas used.